Changing the Game in Ulcerative Colitis: The Impact of Gut-Selective Therapy

Abstract

Given the progressive nature of ulcerative colitis (UC), Prof Colombel argued that effective therapy is warranted early in the disease course, especially for patients judged at a high risk of colectomy. To slow disease progression clinicians should aim for complete recovery or absence of inflammation in the gut mucosa. This goal has recently been recommended by the US Food and Drug Administration (FDA) who advised that endoscopy should be used in conjunction with histology for the assessment of mucosal healing in UC. Considering remission in UC, Prof Feagan explained that while there is clear evidence that endoscopic remission is associated with better outcomes, challenges remain in achieving remission with current agents. Studies show utility for incorporating histopathological activity into clinical trials, but there are concerns regarding the lack of agreement among pathologists. Two newly validated indices for evaluating histologic disease activity in UC (Robarts Histopathology Index [RHI] and Nancy Histopathology Index) open the way for histopathology to be introduced in early drug development. Prof Schreiber reviewed vedolizumab, a gut-selective α4β7 integrin antagonist recommended by the European Crohn’s and Colitis Organisation (ECCO) guidelines as a first-line biologic therapy for the treatment of moderate-to-severe UC. Data from clinical trials showed that vedolizumab has the greatest efficacy in anti-tumour necrosis factor (TNF)-naïve patients and early in the disease course. Histologic healing, reported in >50% of UC patients with endoscopic remission taking vedolizumab, is likely to be a new endpoint in clinical trials. Vedolizumab has a favourable risk-benefit profile, with >77,382 patient years of post-marketing exposure worldwide.1